GLUTAMINE PROTECTS INTESTINAL EPITHELIAL-CELLS - ROLE OF INDUCIBLE HSP70

Glutamine (Gin) protects gut mucosa against injury and promotes mucosa l healing. Because the induction of heat shock proteins (HSP) protects cells under conditions of stress, we determined whether Gin conferred protection against stress in an intestinal epithelial cell line throu gh HSP induction. Gin added to IEC-18 cells induces an increase in HSP 70, a concentration-dependent effect also seen with mRNA. Two forms of injury, lethal heat (49 degrees C) and oxidant, were used, and viabil ity was determined by Cr-51 release. Gin-treated cells were significan tly more resistant to injury. Treatment with 6-diazo-5-oxo-L-norleucin e (DON), a nonmetabolizable analog of Gin, induced HSP70 and protected cells from injury, but less than Gin. These findings suggest that the effects of Gin on HSP70 induction and cellular protection are mediate d by metabolic and nonmetabolic mechanisms. To determine whether HSP i nduction was central to the action of Gin and DON, quercetin, which bl ocks HSP induction, was used. Quercetin blocked HSP70 induction and th e protective effect of Gin and DON. We conclude that the protective ef fects of Gin in intestinal epithelial cells are in part mediated by HS P70 induction.